P-selectin

P-selectin belongs to the family of selectin adhesion molecules, and is expressed by platelets and endothelial cells on stimulation. This pattern of expression may indicate an involvement of this molecule in inflammation and coagulation. Data from mice lacking P-selectin expression confirmed this assumption. In addition, a key role of P-selectin in the formation of tumour metastases has been established. Apparently unrelated, clinical experience has pointed towards a detrimental interaction of inflammation and cancer with thromboembolic diseases and vice versa. Therefore, targeting molecules such as P-selectin contributing to coagulation, inflammation and metastasis may offer novel therapeutic strategies to treat chronic inflammatory diseases and metastatic cancer. The authors aim to critically evaluate the contribution of P-selectin in these diseases, and discuss the value of therapeutic inhibition of P-selectin functions in coagulation, inflammation and metastasis.     

寡糖Lewis A模拟肽对博莱霉素诱导的小鼠急性肺炎症性损伤的抑制作用

目的考察寡糖LewisA模拟肽对肺炎症性损伤的抑制作用。方法采用博莱霉素诱导小鼠肺产生炎症损伤 ,采用病理切片法观察LewisA模拟肽对炎症的影响。结果早期注射寡糖LewisA模拟肽可以抑制博莱霉素诱导的小鼠肺炎症性损伤。结论寡糖LewisA模拟肽可能作为抑制肺炎症性损伤的药物。     

不同病因慢性肝病患者肝组织中IL-10的表达及意义

目的：探讨不同病因的慢性肝病（ CLD）患者肝组织中白细胞介素?10（ IL?10）的表达及其与肝组织炎症和纤维化的关系。方法收集93例CLD患者及23例正常对照肝组织石蜡标本,免疫组织化学方法检测肝组织中IL?10的表达。结果不同病因的CLD患者肝组织中肝小叶及汇管区IL?10的表达均较正常对照明显增高（ P＜0．01）。随着肝脏炎症分级（ G）的增高,CLD患者肝组织内肝小叶及汇管区IL?10的表达逐渐增强,差异有统计学意义。随着肝脏纤维化程度分期（ S）的增高,CLD患者肝组织内肝小叶及汇管区IL?10的表达亦逐渐增高,差异有统计学意义。结论 IL?10可能参与CLD患者肝脏的炎症和纤维化的发生。     

Significant decrease in plasmad‐dimer levels and mean platelet volume after a 3‐month treatment with rosuvastatin in patients with venous thromboembolism

BackgroundInflammation has been considered as a possible mechanism for the initiation and recurrence of venous thromboembolism (VTE). Statins have anti‐inflammatory and potential immune‐modulatory effects, but their effect on plasmad‐dimer levels is controversial.HypothesisIn this study, we aimed to evaluate the impact of rosuvastatin on D‐dimer and other inflammatory serum markers in VTE patients.MethodsWe conducted a prospective, randomized study on 228 patients with VTE. Control group received conventional treatment (warfarin or rivaroxaban), whereas rosuvastatin‐intervention group received rosuvastatin 10 mg daily, in addition to their conventional treatment for 3 months. Serum markers were extracted from both groups at the baseline and 3 months after the beginning of treatment.ResultsAfter 3 months, in patients of the intervention group, there was a statistically significant decrease in levels ofd‐dimer and mean platelet volume (MPV) but no significant change in neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio.ConclusionsOur results showed that a 3‐month treatment with 10 mg rosuvastatin daily can significantly decrease the plasma levels ofd‐dimer and MPV, which would support a potential role of statins to reduce activated systemic inflammation among VTE patients. Such effects can be used to reduce the rate of recurrent VTE in these patients.     

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes

The treatment of nonalcoholic fatty liver disease (NAFLD) remains very challenging. This study investigated the therapeutic effect of galactose oligosaccharide (GOS), an important prebiotic, on NAFLD through in vivo and in vitro experiments and preliminarily explored the mechanism by which GOS improves liver lipid metabolism and inflammation through liver and intestinal microbiological analysis. The results of mouse liver lipidomics showed that GOS could promote body thermogenesis in mice with high-fat and high-sugar diet (HFHSD)-induced NAFLD, regulate lipolysis in liver fat cells, and accelerate glycine and cholesterol metabolism. GOS dose-dependently reduced the contents of total cholesterol (TC) and triglyceride (TG) in cells and reduced the accumulation of lipid droplets in cells. GOS also reduced the Firmicutes/Bacteroidetes ratio and altered the composition of the intestinal microbiota in mice fed a HFHSD. GOS can improve liver lipid metabolism and intestinal structure of NAFLD. These results provide a theoretical and experimental basis supporting the use of GOS as a health food with anti-NAFLD functions.     

CpG寡脱氧核苷酸对慢性哮喘小鼠模型气道炎症的预防作用

目的研究含非甲基化的胞嘧啶-磷酸-鸟嘌呤（CpG）寡脱氧核苷酸（CpG-oligodeoxynueleotides,CpG- ODN）能否预防或减轻慢性哮喘小鼠气道炎症的发生。方法40只雌性C57BL／6小鼠随机均分为4组,A组（慢性哮喘组）、B组（CpG-ODN干预组）和C组（GpC-ODN对照组）分别腹腔注射卵蛋白致敏,然后用卵蛋白雾化吸入激发以制作慢性哮喘模型,D组（生理盐水对照组）用生理盐水进行致敏和激发。B组在致敏同时（d1, d14）和激发阶段（每2周1次）分别给予60μg／mLCpG-ODN腹腔注射,共6次。C组将CpG替换为鸟嘌呤-磷酸-胞嘧啶（GpC）作为对照。在末次激发24 h后,取血测嗜酸粒细胞（eosinophil,EOS）数,血清IgE、IgG1和IgG2α;收集支气管肺泡灌洗液（bronehoalveolar lavage fluid,BALF）作细胞分类计数;测定肺组织中白介素-4 （interleukin-4,IL-4）、白介素-13（interleukin-13,IL-13）和γ-干扰素的mRNA（interferon-γ,IFN-γ）表达量;以及肺组织病理学检查。结果A组外周血EOS数[（89±10）×10^4／mL]、血清IgE值[（279±53）ng／mL）、IgG1（A值2．151±0．628）、IgG2α（A值0．772±0．245）、BALF中EPS（6．3±1．3）]×10^5／mL）及百分比[（18．1±3．0）％]较D组明显增高（P〈0．01）;且肺组织中IL-4、IL-13和IFN-γ等细胞因子mRNA表达量[（分别为（5．72±3．89）×10^-2、（9．45±5．91）×10^-2和（3．23±1．69）×10^-2）]也明显高于D组（P〈0．05）。用CpG-ODN干预后（B组）,除IgG2α（A值1．186±0．414）和IFNγmRNA表达量[（18．91±9．85）×10^-2]增高外（P〈0．05）,其余指标均低于A组（P〈0．05）。C组的上述各指标与A组相比差异均无显著性（P〉0．05）。结论CpG- ODN对小剂量OVA反复激发所致的慢性气道炎症有一定的预防作用。     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.